SUMMARY Until recently, the ability to create specific genetic alterations in mammals was primarily restricted to using homologous recombination in mice. Over the past decade, new developments in genome editing opened the door for introducing targeted changes to the DNA of most species, including humans. New editing techniques rely on the error-prone repair processes nonhomologous-end joining (NHEJ) and microhomology mediated- end joining (MMEJ) to generate small insertions or deletions within a target gene after the creation of a double stranded DNA break, which in turn may lead to a premature stop codon or a nonfunctional protein. Alternatively, a desired specific DNA sequence can be integrated at the site of the DNA lesion through homology-directed repair (HDR). Other systems also have been developed that allow for the modification of a single nucleotide through DNA base editing (DBE), thereby avoiding the creation of double stranded DNA breaks. While these approaches are major advances toward correcting disease-causing inherited mutations in embryos or de novo mutations that occur in a tissue specific manner, there are concerns regarding efficacy and safety. Genome editing methods have the potential to create a ?mosaic? of different mutations, some that may be corrective and some that may be detrimental to cellular function. Another concern includes editing in homologous ?off-target? DNA sequences, which in turn can have negative impacts on the function of an unrelated gene or set of genes. Therefore, it is imperative that a reporter animal is created that can be used to test editing heterogeneity and off-target effects for existing or yet to be developed genome editing techniques that would potentially be used for therapeutic applications. To accomplish this objective, we propose to create a rhesus macaque reporter animal through two complimentary approaches that will provide investigators with the resources needed for assessing the efficiency and specificity of NHEJ-, MMEJ-, HDR-, or DBE-based approaches. We will generate personalized genome assemblies from each reporter animal to facilitate highly accurate detection of subsequent off-target effects. A cohort of animals will be derived that will serve as the foundation for subsequent reporter assessment projects. Importantly, based on the close genetic, physiological, and anatomical relationship with humans, assessment of genome editing activities in these rhesus macaque reporter animals will provide insight into their therapeutic potential.